The broad objective of the proposed research, a continuing study of several years' duration, is to learn more about those metabolic properties of the red cells of man and of other vertebrates which contribute to their viability in vivo and in vitro and which support their function in the transport of oxygen from environment to tissues. An important experimental approach will include analyses by ion-exchange column chromatography, and by other means, of the intracellular intermediates of carbohydrate and nucleotide metabolism, from normal, abnormal and experimentally modified red cells. The proposed study can be subdivided into the following: 1) Metabolic structure and regulation with emphasis on fresh and stored human red cells. 2) Adaptive and evolutionary modifications of red cells of diferent vertebrated animals, with emphasis on those changes which help regulate oxygen transport. 3) Metabolic changes in red cells during their maturation in the bone marrow (mammals), with rat and rabbit the principal models. 4) Metabolic changes of red cells during embryological development, with emphasis on the mammalian fetus using a variety of animals and also on the embyros developing in certain bird and reptilian eggs. 5) Participation of ATP and GTP in the transport of iron into the developing red cell and in the incorporation of iron into hemoglobin. Structure and chemical reactivity of ferric-ATP and -GTP. 6) Metabolism of adenine nucleotide in the circulating red cell of man and experimental mammals. 7) Distribution among red cells, metabolism and regulation of oxygen transport, by inositol polyphosphates.